Role of SHIP in cancer.

The SH2-containing inositol-5'-phosphatase, SHIP (or SHIP1), is a hematopoietic-restricted phosphatidylinositide phosphatase that translocates to the plasma membrane after extracellular stimulation and hydrolyzes the phosphatidylinositol-3-kinase-generated second messenger PI-3,4,5-P(3) to PI-3,4-P(2). As a result, SHIP dampens down PI-3,4,5-P(3)-mediated signaling and represses the proliferation, differentiation, survival, activation, and migration of hematopoietic cells. There are multiple lines of evidence suggesting that SHIP may act as a tumor suppressor during leukemogenesis and lymphomagenesis. Because of its ability to skew macrophage progenitors toward M1 macrophages and naïve T cells toward T helper 1 and T helper 17 cells, SHIP may play a critical role in activating the immune system to eradicate solid tumors. In this review, we will discuss the role of SHIP in hematopoietic cells and its therapeutic potential in terms of suppressing leukemias and lymphomas and manipulating the immune system to combat cancer.